Programmable microcapsules from self-immolative polymers

Article abstract of DOI:10.1021/ja104812p

For the autonomous repair of damaged materials, microcapsules are needed that release their contents in response to a variety of physical and chemical phenomena, not just by direct mechanical rupture. Herein we report a general route to programmable microcapsules. This method creates core-shell microcapsules with polymeric shell walls composed of self-immolative polymer networks. The polymers in these networks undergo a head-to-tail depolymerization upon removal of the triggering end group, leading to breakdown of the shell wall and subsequent release of the capsule's liquid interior. We report microcapsules with shell walls bearing both Boc and Fmoc triggering groups. The capsules release their contents only under conditions known to remove these triggering groups; otherwise, they retain their contents under a variety of conditions. In support of the proposed release mechanism, the capsule shell walls were observed to undergo physical cracking upon exposure to the triggering conditions.

Full text of DOI:10.1021/ja104812p

Published on Web 07/13/2010
Programmable Microcapsules from Self-Immolative Polymers
Aaron P. Esser-Kahn,†,‡ Nancy R. Sottos,§,‡ Scott R. White,|,‡ and Jeffrey S. Moore*,†,‡
Departments of Chemistry, Materials Science and Engineering, and Aerospace Engineering and the Beckman
Institute for AdVanced Science and Technology, UniVersity of Illinois at Urbana-Champaign,
Urbana, Illinois 61801
Received June 2, 2010; E-mail: jsmoore@illinois.edu
Abstract: For the autonomous repair of damaged materials,
microcapsules are needed that release their contents in response
to a variety of physical and chemical phenomena, not just by direct
mechanical rupture. Herein we report a general route to program-
mable microcapsules. This method creates core-shell micro-
capsules with polymeric shell walls composed of self-immolative
polymer networks. The polymers in these networks undergo a
head-to-tail depolymerization upon removal of the triggering end
group, leading to breakdown of the shell wall and subsequent
Figure 1. Schematic of a programmable microcapsule. The capsule shell
wall is a self-immolative cross-linked polymer network (blue) with a loaded
trigger (star). The capsule releases its contents upon activation from a
release of the capsule’s liquid interior. We report microcapsules
with shell walls bearing both Boc and Fmoc triggering groups.
The capsules release their contents only under conditions known
to remove these triggering groups; otherwise, they retain their
contents under a variety of conditions. In support of the proposed
release mechanism, the capsule shell walls were observed to
undergo physical cracking upon exposure to the triggering
conditions.
triggering event. This event removes the head of the polymer (star), initiating
a head-to-tail depolymerization and release of the core contents.
Scheme 1. Synthesis of Self-Immolative Polymers
Autonomous repair of damaged devices remains an ongoing
challenge in the field of materials science. One approach is the
release of compartmentalized chemicals via rupture of microcap-
sules by crack propagation.1 Beyond repair of structural materials,
restoration of other functions such as optical and electronic
properties could benefit from the triggered release of a healing
fluid,2 but the technology for rupturing microcapsules is currently
limited by the need for direct, mechanical interaction between the
capsule and the damage. In ideal self-healing systems, capsules
could release healing agent in response to various physical,
chemical, or biological signals. Nature uses this approach in a
number of healing and regulatory systems where small concentra-
tions of a chemical signal are turned into large-scale responses.15
Synthetically, the concept of stimuli-triggered release was first
demonstrated with lipid vesicles.3 However, polymeric microcap-
sules are stronger, more chemically resistant, and able to contain
larger volumes4 than liposomes, making them attractive for
materials applications. “Triggerable” microcapsules that are ruptured
by light, enzymes, or chemical reduction5 have been reported. Here
we present a general approach to programmable microcapsules that
release their core when triggered by a specific event that ruptures
the shell wall.
networks that undergo a head-to-tail depolymerization upon
removal of a triggering end group.6 The “trigger” is a carbamate-
based protecting group, making this method highly general. In
this work, we have synthesized capsules that are sensitive to
either HCl or piperidine, but many other variations can easily
be imagined.
Construction of the self-immolative polymer followed methods
similar to those of Sagi et al.6 Briefly, monomer 1 bearing a tert-
butyldimethylsilyl (TBDMS)-protected9 pendant alcohol and a
masked isocyanate was created. This was then mixed with the
phenyl carbamate of aminobenzyl alcohol (2) in a 3:7 ratio and
polymerized by addition of catalytic dibutyl tin dilaurate (DBTL)
to create a metastable polyurethane. Trigger-loaded polymers were
created by capping the terminal isocyanate through addition of an
unique alcohol to form a carbamate protecting group [SI-6, SI-7,
where SI-n refers to compound n in the Supporting Information
(SI)]) (Scheme 1). The linear polymers were characterized by NMR
spectroscopy and gel-permeation chromatography (GPC) (see the
SI).
Depolymerization of the linear polymers was monitored by GPC.
Polymers terminated with a Boc10 or Fmoc11 trigger were exposed
to conditions known to remove that group (Boc, 1:1 TFA/CH2Cl2;
Fmoc, 10% piperidine in THF) as well as orthogonal, unreactive
conditions (e.g., Boc exposed to 10% piperidine in THF). The
depolymerization reaction was allowed to proceed over 48 h. In
the presence of triggering conditions, the polymers showed a large
molecular weight reduction. They did not, however, show the same
reduction in the opposing triggering conditions (Figure 2). These
As other triggerable shell walls require specific syntheses, we
sought to develop a general method for core-shell microcapsules
by embedding a chemical trigger in the shell wall (Figure 1). The
capsule shell wall is constructed from self-immolative polymer
† Department of Chemistry.
‡ Beckman Institute for Advanced Science and Technology.
§ Department of Materials Science and Engineering.
| Department of Aerospace Engineering.
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10.1021/ja104812p  2010 American Chemical Society

C O M M U N I C A T I O N S
Figure 4. Microcapsule morphology. (a) Fluorescence microscopy images
and (b) optical microscopy images of Boc microcapsules.
Figure 2. Triggered depolymerization of polymers. (a, b) Scheme depicting
(a) the triggers and (b) the polymers and disassembly chemistry. (c) GPC
traces showing disassembly of the polymers after removal of the triggers.
Green: 10% piperidine, THF, 15 min. Red: 1:1 TFA/CH2Cl2, 15 min. Blue:
unexposed polymer.
Figure 5. Release of core contents. (a) Percentage of core released after
48 h in triggering solution for capsule sizes of 5-40 µm. Blue: 4 M aqueous
HCl with 10% EtOH. Red: 5% piperidine in THF. Percentage of core
released was calculated as the integral of the GC peak relative to that for
manual rupture. (b) Release profile of the two triggers (Boc, Fmoc) in their
respective triggering solutions. The final data point was set to 100% to
facilitate interpretation.
Figure 3. Synthesis of microcapsules. The trigger-loaded polymer was
treated with TBAF in order to remove the TBDMS protecting group.
The free alcohols were then reacted with 2,4-TDI to form a prepolymer
for microcapsule formation. Microcapsules were formed by an interfacial
polymerization reaction between the isocyanates and 1,4-butanediol.
HCl with 10% EtOH and to 5% piperidine in THF, conditions
known to trigger the Boc and Fmoc protecting groups, respec-
tively. In order to monitor the triggered release of the micro-
capsules’ content, we measured the amount of core contents
(EPA) released after 48 h using gas chromatography (GC)12 after
immersion in each of the different triggering solutions. The
results are presented as the percentage of core released relative
to that released upon manual rupture of the capsules (Figure
5a). Capsules released their core contents upon exposure only
to the conditions specific to the trigger removal, while capsules
exposed to conditions in which the trigger is unreactive showed
little to no release of core contents. Additionally, control capsules
without a self-immolative shell wall (Control) did not show
release under any triggering conditions.
Release profiles of Boc and Fmoc microcapsules were monitored
by GC over the same 48 h period. Release of core material is
displayed as a percentage of the final 48 h data point (Figure 5b).
Fmoc capsules exposed to 5% piperidine released their content
slightly faster than Boc capsules exposed to 4 M HCl, with complete
release in 24 h. This effect may be a result of the solvent dependence
of the azaquinone methide elimination.14 We will investigate this
phenomenon in future work.
We examined the capsules’ shell morphology to confirm that
rupture of the shell wall was the mechanism of release (Figure 6).
Following exposure to the triggering conditions, SEM was used to
visualize changes in shell-wall morphology. Microcapsules exposed
to their matching triggering conditions appear cracked and in some
instances deflated, whereas capsules exposed to the nonmatching
triggering conditions appear unaffected. In great contrast, the
morphology of the control capsules was unaffected under either
set of triggering conditions (Figure 6). Combining these observa-
tions with the core release data, we conclude that triggering
conditions caused a chemically specific depolymerization of the
polymer shell wall coincident with release of the core contents.
results show that removal of the trigger group initiates depolym-
erization of the linear polymer.
The trigger-loaded polymers were transformed into microcapsules
by conversion into a reactive prepolymer.12 The TBDMS group
was removed from the polymers (SI-10, SI-11), and the polyols
were cross-linked and converted to isocyanates by reaction with
excess 2,4-toluene diisocyanate (2,4-TDI) in cyclohexanone (Figure
3). A molecular weight increase was observed by GPC (see the
SI).
Microcapsules were synthesized via an interfacial polymerization
method as previously described.8 To a solution of water with gum
arabic (surfactant and viscosity modifier) was added trigger-loaded
“prepolymer” (SI-8, SI-9) dissolved in the core solvent [ethyl
phenylacetate (EPA)]. Butanediol was added to the resulting
emulsion as a chain extender, and the solution was heated to 70 °C
for 1.5 h (Figure 3). We synthesized Boc and Fmoc microcapsules,
whose shell walls consisted of polymer networks terminated with
Boc and Fmoc groups, respectively. Capsules were routinely
produced in the 5-40 µm size range. The size and shell-wall
morphology were determined by fluorescence, optical, and scanning
electron microscopy (Figures 4 and 6). We found that the capsules
have a distinctive “wrinkled” appearance. This morphology did not
occur under identical capsule formation conditions using the control
polymer Desmodur L75, a commercially available prepolymer
composed of cross-linked 2,4-TDI (affording microcapsules des-
ignated as Control), indicating that it is unique to the trigger-loaded
polymer (Figure 6). Additionally, the capsule shell wall was
fluorescent, indicating the presence of the trigger-loaded polymers
at the shell wall.13
We hypothesized that the capsules loaded with a given trigger
would rupture upon exposure to conditions specific to the
removal of that group (hereafter called triggering conditions).
Boc and Fmoc microcapsules were both exposed to 4 M aqueous
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C O M M U N I C A T I O N S
the U.S. Department of Energy, Office of Science, Office of Basic
Energy Sciences, under Award DE-AC02-06CH11357 9F-31921.
This work was supported by the Air Force Office of Scientific
Research MURI (Grant F49550-05-1-0346). The authors also
acknowledge Mary Caruso, David McIlroy, Ben Blaisik, Brett
Bierman, Susan Odom, Marta Baginska, Doug Davis, and the entire
Autonomous Materials Systems Group for helpful discussions
relating to this project. The authors thank Dorothy Loudermilk for
assistance in figure creation.
Supporting Information Available: Experimental procedures,
synthesis of small molecules and polymers, triggering conditions,
UV-vis spectra, controls, additional GPC traces, TGA and GC data,
and details of the synthesis of capsules. This material is available free
of charge via the Internet at http://pubs.acs.org.
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In view of the time scale on which the linear polymer depoly-
merizes (Figure 2), it is surprising that the capsule shell walls remain
intact under these conditions. The enhanced capsule stability may
be due to the solid-phase nature of the shell wall. Moreover,
introduction of trace quantities of units that disrupt the depolym-
erization reaction cannot be ruled out at this time. Further research
on enhancing the rate of capsule rupture is ongoing and will be
reported in due course.
In conclusion, we have outlined a general route to programmable
microcapsules. We have demonstrated the synthesis of trigger-
loaded self-immolative polymers and their subsequent transforma-
tion into core-shell microcapsules. We have shown that both the
polymer and capsules depolymerize only when exposed to matching
triggering conditions and that nontriggering conditions do not cause
the capsules to release their core contents or to change their
morphology. There are potentially over 100 protecting groups that
are synthetically amenable to our method7 and still others that could
be triggered enzymatically.8 We envision that this will allow the
rapid prototyping of capsules that can be made to release their
contents upon activation by various chemical, physical, or biological
stimuli. These types of “on-demand” chemical systems could find
use in diverse areas ranging from drug delivery to self-healing Li
ion batteries that are safer and longer-lasting.
Acknowledgment. This material is based upon work supported
as part of the The Center for Electrochemical Energy Storage-
Tailored Interfaces, an Energy Frontier Research Center funded by
JA104812P
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